Addressing gastric cancers, a leading cause of cancer deaths in Asia
By Joseph Blanchette
Gastric cancer is the third-leading cause of cancer-related deaths in the world, with more than 50 percent of cases occurring in East Asia. About 17 million Americans are of Asian descent, putting them at increased genetic risk for the disease. Researchers at The Jackson Laboratory are making significant breakthroughs in understanding and targeting gastric cancers.
The scientific director of JAX Genomic Medicine, Charles Lee, Ph.D., FACMG, is recognized worldwide for his discovery of widespread structural variation in the human genome, in the form of copy number variation (CNV). This is a state in which cells have an abnormal number of copies of DNA sections, sometimes associated with susceptibility or resistance to disease, including cancer.
Lee is also a distinguished professor at Ewha Womans University in Seoul, South Korea. In collaboration with Han-Kwan Yang, M.D., Ph.D., one of the worlds's foremost clinical researchers in gastric cancer research at Seoul National University Hospital in South Korea, the Lee Lab published a study in The Proceedings of the National Academy of Sciences (PNAS 112: 12492-7, 2015) of gastric cancers specimens from 103 patients and identified two new potential targets for some of the gastric cancers. The study approach itself offers a blueprint for expediting the discovery and validation of new drugs for this disease.
"Our study has revealed two potential novel molecular mechanisms for the treatment of subsets of gastric cancers," Lee says. "Our approach of integrating genomic molecular profiling and PDX mouse models provides a valuable platform for novel drug-target discovery and validation."
JAX Professor, Director of Genome Sciences and Florine Deschenes Roux Chair Yijun Ruan, Ph.D., has a grant from the National Cancer Institute to explore the role of noncoding RNAs (ncRNAs) in cancers, including gastric cancer, and other diseases. Most RNAs manufacture proteins from the Blueprint" provided by DNA, but there are many kinds of ncRNAs that carry out other vital roles in cells. Ruan and his lab are using new technologies to identify novel ncRNAs and the interactions between ncRNAs and their target DNAs. Because ncRNAs are associated with diseases such as cancers, such novel ncRNAs and their target DNAs have the potential to be diagnostic biomarkers and novel genomic therapeutic targets for disease.
As published in Cell Reports (Cell Reports 12:272, 2015), Ruan's lab identified five recurrent fusion genes in the gastric cancers of 15 Southeast Asian patients. They discovered that one of these fusion genes, CLDN18-ARHGAP26, appears to lead to cellular changes involved in acute gastritis and cancer.